PROJECT SUMMARY Project Title: Production Technology for Recombinant Intravenous Immunoglobulin Organization: GigaGen Inc. PI: David S. Johnson, Ph.D. Intravenous immunoglobulin, or IVIg, is a pool of antibodies isolated from the plasma of thousands of donors. IVIg therapy is used for several indications, including B cell chronic lymphocytic leukemia (CLL), autoimmune neuropathy, and primary immunodeficiency (PID). IVIg sales are $9 billion worldwide and growing at 8-10% per year, due to an aging population and ever-expanding therapeutic indications. Conventional methods for IVIg production threaten continued expansion of IVIg therapy because of supply chain risk, impurities, and batch-to- batch variation. Recombinant IVIg, or rIVIg, could solve all of the problems with the conventional plasma product. However, until recently there has been no technology that could capture highly diverse native immune repertoires and recreate them in vitro. In our SBIR Phase I, we used our GigaLink? molecular genomics technology to build DNA libraries of natively paired Ig, and then express them in Chinese hamster ovary (CHO) cells to produce the world's first rIVIg product. In our corresponding SBIR Phase II Renewal, we take steps to further develop the therapeutic product by building a library that meets FDA guidelines, scaling protein production, and benchmarking the product against conventional IVIg. After completing this SBIR Phase II, we will have sufficient data for a pre-IND meeting with the FDA for the world?s first recombinant IVIg drug. Though PID will be the primary clinical indication for subsequent clinical studies, the drug could eventually be used for other kinds of immunocompromised patients, such as transplant recipients. Finally, our manufacturing approach could be used to combat emerging pathogens, i.e., for West Nile rapid response.